We propose to carry out investigations of physical mechanisms and conditions for changes in biological systems produced by ultrasound. Experimental work on selected cellular, intracellular and macromolecular systems will be carried out in collaboration between physically and biologically trained scientists. Emphasis will be placed on design of experiments according to available knowledge, and analysis of results to determine basic principles involved. Physical theory will be developed where required, and experiments on model systems carried out to test hypotheses. Specific experiments are proposed to elucidate the cause-effect relationships of non-thermal mechanisms of ultrasound, such as acoustic cavitation, in producing changes in blood cells, including erythrocytes, platelets and lympohocytes, by employing sensitive assay techniques in conjunction with special, low-intensity forms of stable cavitation. The broad aim is to develop methods for calculating dose parameters (frequency, amplitude-distribution or intensity-distribution, pulse regime, time of irradiation, etc.) of an ultrasonic field which lead to specific changes in biological systems. Such methods and information are of critical significance in the rapidly growing field of medical ultrasonics. We expect our work to be part of a wide-ranging effort to determine the safety of diagnostic procedures and the efficacy of therapeutic treatment with ultrasound, involving investigators at a number of institutions. Our biophysical approach, using relatively simple biological units and models is meant to guide and complement other work with more complex systems, by providing basic insights into the etiology of biological effects of ultrasound.